Predictive factors for late cervical metastasis in stage I and II squamous cell carcinoma of the lip.

PURPOSE: Many authors have described clinicopathologic parameters as factors related to cervical lymph node metastasis development in CN0 stage lip cancer. However, predictive factors for occult lymph node metastasis and criteria for elective neck dissection, especially for early tumour, remain undefined. METHODS: A multi-institutional study with 193 consecutive patients with early lip SCC treated from January 1990 to March 2006 was carried out retrospectively to determine factors predicting occult metastasis. RESULTS: The overall late LNM rate was 13% (25/193). In the multivariate logistic regression study, tumour size and pattern of tumour invasion were factors related to the occurrence of late LNM with rates of sensitivity, specifity and accuracy for occult LNM prediction of 50%, 89.5% and 87%, respectively. CONCLUSION: Our results indicate that patients with stage I and II SCC of the lip with tumour size greater than 18 mm and more aggressive pattern of invasion must be considered a high-risk group for LNM and an END should be performed.

Management of the facial nerve in parotid cancer: preservation or resection and reconstruction.

PURPOSE: Management of the facial nerve is instrumental in the surgical treatment of parotid cancer. METHODS: A literature search was conducted using PubMed and ScienceDirect database. A total of 195 articles were finally included into the analysis, based on relevance, scientific evidence and actuality. RESULTS: In the majority of cases the facial nerve is not involved by tumor. In these cases, identification and preservation of the nerve, in addition to complete tumor removal, are essential for successful surgery. When the nerve is infiltrated by tumor, the affected portion of the nerve must be resected as part of radical parotidectomy. Primary nerve reconstruction or other reanimation techniques give the best long-term functional and cosmetic results. A comprehensive diagnostic evaluation with current imaging and electrophysiological studies will provide the surgeon with the best knowledge of the relationship of the facial nerve to the tumor. Several standardized methods are helpful in finding, dissecting and preserving the nerve during parotid cancer surgery. When radical parotidectomy is indicated, the initial diagnostic work-up can assist in defining the need for adjuvant postoperative therapy and facial reanimation. The aim of rehabilitation is to restore tone, symmetry, and movement to the paralyzed face. CONCLUSIONS: The surgical management of facial paralysis has undergone many improvements in recent years. This review gives an overview of recent advances in the diagnostic work-up, surgical techniques and any necessary rehabilitation of the facial nerve in parotid cancer surgery.

Minimum nodal yield in oral squamous cell carcinoma: defining the standard of care in a multicenter international pooled validation study.

PURPOSE: There is evidence to suggest that a nodal yield <18 is an independent prognostic factor in patients with clinically node negative (cN0) oral squamous cell carcinoma (SCC) treated with elective neck dissection (END). We sought to evaluate this hypothesis with external validation and to investigate for heterogeneity between institutions. PATIENTS AND METHODS: We analyzed pooled individual data from 1,567 patients treated at nine comprehensive cancer centers worldwide between 1970 and 2011. Nodal yield was assessed with Cox proportional hazard models, stratified by study center, and adjusted for age, sex, pathological T and N stage, margin status, extracapsular nodal spread, time period of primary treatment, and adjuvant therapy. Two-stage random-effects meta-analyses were used to investigate for heterogeneity between institutions. RESULTS: In multivariable analyses of patients undergoing selective neck dissection, nodal yield <18 was associated with reduced overall survival [hazard ratio (HR) 1.69; 95 % confidence interval (CI) 1.22-2.34; p = 0.002] and disease-specific survival (HR 1.88; 95 % CI 1.21-2.91; p = 0.005), and increased risk of locoregional recurrence (HR 1.53; 95 % CI 1.04-2.26; p = 0.032). Despite significant differences between institutions in terms of patient clinicopathological factors, nodal yield, and outcomes, random-effects meta-analysis demonstrated no evidence of heterogeneity between centers in regards to the impact of nodal yield on disease-specific survival (p = 0.663; I (2) statistic = 0). CONCLUSION: Our data confirm that nodal yield is a robust independent prognostic factor in patients undergoing END for cN0 oral SCC, and may be applied irrespective of the underlying patient population and treating institution. A minimum adequate lymphadenectomy in this setting should include at least 18 nodes.

Recurrent copy number gains of ACVR1 and corresponding transcript overexpression are associated with survival in head and neck squamous cell carcinomas.

AIMS: This study aimed to evaluate the copy number alteration on 2q24, its association with ACVR1 transcript expression and the prognostic value of these data in head and neck squamous cell carcinomas. METHODS AND RESULTS: Twenty-eight samples of squamous cell carcinoma were evaluated by fluorescence in situ hybridization (FISH) using the probes RP11-546J1 (2q24) and RP11-21P18 (internal control). Significant gains at 2q24 were detected in most cases at frequencies varying from 3 to 35%. ACVR1 gains and amplifications were associated with longer overall survival (P = 0.022). ACVR1 mRNA expression analysis in 78 cases revealed overexpression in 44% (34 of 78) of these tumours, suggesting that gene copy number alterations could be involved in gene overexpression. In laryngeal carcinomas, overexpression of ACVR1 mRNA levels was associated with longer overall survival (P = 0.013). Multivariate analysis revealed that ACVR1 is an independent prognostic marker in laryngeal carcinomas (P = 0.012, hazard ratio = 0.165, 95% confidence interval =0.041-0.668). CONCLUSIONS: These findings suggest that copy number alterations at 2q24 can be involved in ACVR1 overexpression, which is associated with longer overall survival in laryngeal carcinomas. To our knowledge, this is the first report indicating the relevance of ACVR1 expression in head and neck cancers.

Epigenetic silencing of CRABP2 and MX1 in head and neck tumors.

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease affecting the epithelium of the oral cavity, pharynx and larynx. Conditions of most patients are diagnosed at late stages of the disease, and no sensitive and specific predictors of aggressive behavior have been identified yet. Therefore, early detection and prognostic biomarkers are highly desirable for a more rational management of the disease. Hypermethylation of CpG islands is one of the most important epigenetic mechanisms that leads to gene silencing in tumors and has been extensively used for the identification of biomarkers. In this study, we combined rapid subtractive hybridization and microarray analysis in a hierarchical manner to select genes that are putatively reactivated by the demethylating agent 5-aza-2'-deoxycytidine (5Aza-dC) in HNSCC cell lines (FaDu, UM-SCC-14A, UM-SCC-17A, UM-SCC-38A). This combined analysis identified 78 genes, 35 of which were reactivated in at least 2 cell lines and harbored a CpG island at their 5' region. Reactivation of 3 of these 35 genes (CRABP2, MX1, and SLC15A3) was confirmed by quantitative real-time polymerase chain reaction (PCR; fold change, >or=3). Bisulfite sequencing of their CpG islands revealed that they are indeed differentially methylated in the HNSCC cell lines. Using methylation-specific PCR, we detected a higher frequency of CRABP2 (58.1% for region 1) and MX1 (46.3%) hypermethylation in primary HNSCC when compared with lymphocytes from healthy individuals. Finally, absence of the CRABP2 protein was associated with decreased disease-free survival rates, supporting a potential use of CRABP2 expression as a prognostic biomarker for HNSCC patients.

Nomogram for deciding adjuvant treatment after surgery for oral cavity squamous cell carcinoma.

BACKGROUND: The application of appropriate adjuvant treatment after surgery for oral cavity squamous cell carcinoma (OCSCC) is predicated on accurate patient risk stratification. METHODS: A nomogram for estimating locoregional recurrence-free survival (LRFS) after treatment of OCSCC was constructed from a cohort of 590 patients with OCSCC who were treated at Memorial Sloan-Kettering Cancer Center (MSKCC). The nomogram was validated using a series of 417 patients with OCSCC who were treated at Hospital do Cancer AC Camargo (HACC) in São Paulo, Brazil. RESULTS: Despite significant differences between the MSKCC and HACC cohorts, the nomogram was able to predict LRFS from OCSCC with a concordance index of 0.693. Further statistical analysis showed that the nomogram was well calibrated. CONCLUSIONS: This preliminary nomogram is the first prognostic model developed and externally validated to predict the likelihood of LRFS after treatment for an individual patient with OCSCC and may have practical utility for deciding adjuvant treatment.

Differential expression of IGFBP-5 and two human ESTs in thyroid glands with goiter, adenoma and papillary or follicular carcinomas.

Here, we describe the identification of three human genes with altered expression in thyroid diseases. One of them corresponds to insulin-like growth factor binding protein 5 (IGFBP5), which has already been described as over expressed in other cancers and, for the first time, is identified as overexpressed in thyroid tumors. The other genes, named 44 and 199, are ESTs with yet unknown function and were mapped on human chromosomes seven and four, respectively. We determined by RT-PCR the expression level of these genes in ten samples of disease-free thyroid, ten of goiter, nine of papillary carcinoma, ten of adenoma and seven of follicular carcinoma and the significance of observed differences was statistically determined. IGFBP-5 and gene 44 were significantly overexpressed in papillary carcinoma when compared to normal and goiter. Genes 44 and 199 were differentially expressed in follicular carcinoma and adenoma when compared to normal thyroid tissue.